The invention relates generally to treating nanoparticles, particularly those based on transition metal oxides, to render them sufficiently hydrophilic to form stable aqueous suspensions and therefore be useful in applications requiring hydrophilicity such as contrast agents in diagnostic imaging such as MRI and X-ray, to the hydrophilic nanoparticles resulting from said treatment, to said stable aqueous suspensions and to the use of said hydrophilic nanoparticles as contrast agents in said imaging. Nanoparticles, i.e. particles whose diameters are appropriately measured in nanometers, have been considered for a wide variety of end uses. Some of these uses require some degree of hydrophilicity but the material upon which some nanoparticles are based may lack this attribute. For instance, nanoparticles with appropriate imaging properties for use as contrast agents for MR and X-ray imaging are typically based on transition metal oxides which lack suitable hydrophilicity. Therefore efforts have been made to modify the surface properties of these nanoparticles to be more compatible with aqueous media and give these nanoparticles the ability to form stable aqueous suspensions. However, in some applications such as use as contrast agents it is also desirable that the nanoparticles have a monodisperse particle size distribution and any surface treatment that results in a polydisperse particle size distribution such as non-uniform aggregation by complexation in a biological matrix based on carbohydrates with carboxylate groups is problematic. In addition, in some applications such as in vivo use as contrast agents it is desirable that the surface treatment have a well defined reproducible structure and be amenable to safety testing. Silane based surface treatments can be problematic because they can undergo self condensation that interferes with these goals.
In addition, there has been a need for hydrophilic nanoparticles that do not suffer a degradation of their hydrophilicity as a result of purification and display suspension stability in aqueous mediums containing electrolytes. For instance, in the preparation of contrast agents for in vivo use in human subjects the candidate nanoparticles would typically be subjected to filtration and be expected to show suspension stability in isotonic aqueous media, i.e. media containing about 150 mM NaCl. There have been efforts to use the adhesion of phosphates for transition metal oxides to impart this type of hydrophilicity to nanoparticles using phosphate based materials alone, such as polyphosphoric acid, or linked to hydrophilic moieties, such as polyethylene glycol. In this regard, there is a preference for hydrophilic moieties with an essentially neutral zeta potential for in vivo use in human subjects to avoid undesirable interactions with human tissue. However, such efforts have not yielded so hydrophilically modified nanoparticles that display the desired stability as a colloidal suspension in a 150 mM NaCl aqueous medium after filtration. For instance, such efforts have not yielded suspensions which display an essentially stable (no increase in hydrodynamic diameter (DH)) particle size as measured by dynamic light scattering (DLS) after tangential flow filtration with a 30 kDa cut off and storage for more than a week in such an aqueous medium.